rs1400526873

Variant names:

• chr1-27960313-C-A
• rs1400526873
• NM_018053.4:c.244C>A

Your query was ambiguous. Multiple possible variants found:

• chr1-27960313-C-A
• chr1-27960313-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_018053.4(XKR8):​c.244C>A​(p.Arg82Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,216 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R82C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: XKR8 NM_018053.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.234
• Publications: 0 publications found

Genes affected

XKR8 (HGNC:25508): (XK related 8) Enables phospholipid scramblase activity. Involved in engulfment of apoptotic cell; phosphatidylserine exposure on apoptotic cell surface; and positive regulation of myoblast differentiation. Located in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000227050 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08054194).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018053.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	XKR8	NM_018053.4	MANE Select	c.244C>A	p.Arg82Ser	missense	Exon 1 of 3	NP_060523.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	XKR8	ENST00000373884.6	TSL:1 MANE Select	c.244C>A	p.Arg82Ser	missense	Exon 1 of 3	ENSP00000362991.5	Q9H6D3
	XKR8	ENST00000675575.1		c.244C>A	p.Arg82Ser	missense	Exon 1 of 4	ENSP00000502552.1	A0A6Q8PH47
	XKR8	ENST00000675759.1		c.-101+573C>A		intron	N/A	ENSP00000502285.1	A0A6Q8PGH8

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152216 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1280968 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 627222

African (AFR) AF: 0.00 AC: 0 AN: 25462

American (AMR) AF: 0.00 AC: 0 AN: 19302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18894

East Asian (EAS) AF: 0.00 AC: 0 AN: 30972

South Asian (SAS) AF: 0.00 AC: 0 AN: 64284

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 31098

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4384

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1033396

Other (OTH) AF: 0.00 AC: 0 AN: 53176

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152216 Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1 AN XY: 74366

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000241 AC: 1 AN: 41466

American (AMR) AF: 0.00 AC: 0 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4838

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68040

Other (OTH) AF: 0.00 AC: 0 AN: 2090

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	2.5
DANN	Benign	0.78
DEOGEN2	Benign	0.018	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.078	N
LIST_S2	Benign	0.33	T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.081	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.5	L
PhyloP100		0.23
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	0.0	N
REVEL	Benign	0.092
Sift	Benign	0.82	T
Sift4G	Benign	0.30	T
Polyphen		0.053	B
Vest4		0.066
MutPred		0.58		Loss of helix (P = 0.028)
MVP		0.055
MPC		0.50
ClinPred		0.067	T
GERP RS		0.35
PromoterAI		-0.00080	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.071
gMVP		0.14
Mutation Taster		=95/5	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1400526873; hg19: chr1-28286824;